| Title: |
Involvement of Type I Interferon Signaling in Muscle Stem Cell Proliferation During Dermatomyositis |
| Authors: |
Gallay, Laure; Fermon, Cécile; Lessard, Lola; Weiss-Gayet, Michèle; Viel, Sébastien; Streichenberger, Nathalie; Corpet, Armelle; Mounier, Rémi; Gitiaux, Cyril; Mouchiroud, Guy; Chazaud, Bénédicte |
| Contributors: |
Hôpital Edouard Herriot CHU - HCL; Hospices Civils de Lyon (HCL); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon; Institut NeuroMyoGène - Appui à la recherche (INMG-AR); Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Centre International de Recherche en Infectiologie (CIRI); École normale supérieure de Lyon (ENS de Lyon); Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Hôpital Necker - Enfants Malades AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Institut Mondor de Recherche Biomédicale (IMRB); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) |
| Source: |
ISSN: 0028-3878. |
| Publisher Information: |
CCSD; American Academy of Neurology |
| Publication Year: |
2022 |
| Collection: |
Université Jean Monnet – Saint-Etienne: HAL |
| Subject Terms: |
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology; [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]; [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity |
| Description: |
International audience ; Background and objective: The idiopathic inflammatory myopathy Dermatomyositis (DM) is an acquired disease that combines muscle, lung and skin impairments. DM patients show a wide range of severity of proximal skeletal muscle weakness, associated with inflammatory infiltrates, vasculitis and capillary dropout, perifascicular myofiber atrophy. Moreover, DM muscles show signs of muscle regeneration. Since muscle stem cells (MuSCs) are responsible for myofiber repair, we asked wether the proliferative properties of muscle stem cells (MuSCs) are altered in DM muscle. We investigated the role of type-I interferon (IFN-I) in this process since DM is associated with sustained inflammation with high IFN-I levels.Methods: MuSCs isolated from normal, adult and juvenile DM muscles were grown in culture and were analyzed in vitro for their proliferating properties, their myogenic capacities and their senescence. Gain and loss of function experiments were performed to assess the role of IFN-I signaling in the prolfierative capacities of MuSCs. Results: MuSCs derived from 8 DM adult patients (DM-MuSCs) (5 severe form and 3 mild form, established from histological evaluation), from 3 juvenile DM patients and from normal muscle were used to analyze their myogenesis in vitro. DM-MuSCs exhibited strongly reduced proliferating capacities as compared with healthy MuSCs (-31 to -43% for severe and mild DM, respectively), leading to poor myotube formation (-36 to -71%). DM-MuSCs were enriched in senescent, beta-galactosidase positive cells, explaining partly the proliferation defect. Gain and loss of function experiments were performed to assess the role of IFN-I on the proliferative capacity of MuSCs. High concentrations of IFN-I decreased the proliferation of healthy MuSCs. Similarly, conditioned-medium from DM-MuSCs decreased the proliferation of healthy MuSC (-15 to -22%), suggesting the delivery of an autocrine effector. Then, pharmacological blockade of the IFN signaling (using ruxolitinib or ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1212/WNL.0000000000200271 |
| Availability: |
https://hal.science/hal-04830900; https://hal.science/hal-04830900v1/document; https://hal.science/hal-04830900v1/file/NEUROLOGY-2021-177973v2-Chazaud%281%29.pdf; https://doi.org/10.1212/WNL.0000000000200271 |
| Rights: |
http://creativecommons.org/licenses/by-nc-nd/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.8A78C62E |
| Database: |
BASE |